Here, plant HAM proteins are shown to physically interact with the transcription factor WUSCHEL and the related WOX proteins, with this interaction driving downstream transcriptional programs and determining the activities of stem cells. Postembryonic development of above-ground tissues and of roots of plants depends on stem cells in the shoot and root apical meristems, respectively. The transcription factor WUSCHEL (WUS) and the related WOX proteins are known to be involved in the specification and maintenance of stem cells within all meristems throughout the plant kingdom. The HAIRY MERISTEM (HAM) family of transcription regulators is known to contribute to shoot stem cell function in certain plant species. The present paper shows that WOX and HAM family proteins act together to control the production of all types of stem cells in diverse niches in Arabidopsis, and that WUS and HAM share some common targets in vivo. Differences in the combined expression patterns of WOX and HAM family members appear to determine the formation of diverse stem cell niche locations. These findings demonstrate how co-operative transcriptional regulators drive common regulatory pathways and point to mechanisms underlying the evolution of stem cell regulation in plants. Plant stem cells in the shoot apical meristem (SAM) and root apical meristem are necessary for postembryonic development of aboveground tissues and roots, respectively, while secondary vascular stem cells sustain vascular development1,2,3,4. WUSCHEL (WUS), a homeodomain transcription factor expressed in the rib meristem of the Arabidopsis SAM, is a key regulatory factor controlling SAM stem cell populations5,6, and is thought to establish the shoot stem cell niche through a feedback circuit involving the CLAVATA3 (CLV3) peptide signalling pathway7. WUSCHEL-RELATED HOMEOBOX 5 (WOX5), which is specifically expressed in the root quiescent centre, defines quiescent centre identity and functions interchangeably with WUS in the control of shoot and root stem cell niches8. WOX4, expressed in Arabidopsis procambial cells, defines the vascular stem cell niche9,10,11. WUS/WOX family proteins are evolutionarily and functionally conserved throughout the plant kingdom12 and emerge as key actors in the specification and maintenance of stem cells within all meristems13. However, the nature of the genetic regime in stem cell niches that centre on WOX gene function has been elusive, and molecular links underlying conserved WUS/WOX function in stem cell niches remain unknown. Here we demonstrate that the Arabidopsis HAIRY MERISTEM (HAM) family of transcription regulators act as conserved interacting cofactors with WUS/WOX proteins. HAM and WUS share common targets in vivo and their physical interaction is important in driving downstream transcriptional programs and in promoting shoot stem cell proliferation. Differences in the overlapping expression patterns of WOX and HAM family members underlie the formation of diverse stem cell niche locations, and the HAM family is essential for all of these stem cell niches. These findings establish a new framework for the control of stem cell production during plant development.

Enough but not too many stem cells: In the shoot apical meristem of plants, just the right number of stem cells generates a steady supply of cells with which to build differentiated tissues. Too few stem cells, and the plant cannot grow. Too many, and growth runs amok. Zhou et al. analyzed the controls on stem cell proliferation. They found that the HAIRY MERISTEM proteins define a domain within which WUSCHEL (WUS) cannot work, but beyond which WUS is left free to promote stem cell proliferation. Science , this issue p. 502

In multicellular organisms, a long-standing question is how spatial patterns of distinct cell types are initiated and maintained during continuous cell division and proliferation. Along the vertical axis of plant shoot apical meristems (SAMs), stem cells are located at the top while cells specifying the stem cells are located more basally, forming a robust apical-basal pattern. We previously found that in Arabidopsis SAMs, the HAIRY MERISTEM (HAM) family transcription factors form a concentration gradient from the epidermis to the interior cell layers, and this gradient is essential for the stem cell specification and the apical-basal patterning of the SAMs. Here, we uncover that epidermis specific transcription factors, ARABIDOPSIS THALIANA MERISTEM LAYER 1 (ATML1) and its close homolog, define the concentration gradient of HAM in the SAM through activating a group of microRNAs. This study provides a molecular framework linking the epidermis-derived signal to the stem cell homeostasis in plants.