Emerging Roles of Adipose Progenitor Cells in Tissue Development, Homeostasis, Expansion and Thermogenesis

Abstract

Stem or progenitor cells are an essential component for the development, homeostasis, expansion, and regeneration of many tissues. Within white adipose tissue (WAT) reside vascular-resident adipose progenitor cells (APCs) that can proliferate and differentiate into either white or beige/brite adipocytes, which may control adiposity. Recent studies have begun to show that APCs can be manipulated to control adiposity and counteract 'diabesity'. However, much remains unknown about the identity of APCs and how they may control adiposity in response to homeostatic and external cues. Here, we discuss recent advances in our understanding of adipose progenitors and cover a range of topics, including the stem cell/progenitor lineage, their niche, their developmental and adult roles, and their role in cold-induced beige/brite adipocyte formation.

Keywords: adipose tissue; beige/brite adipocytes; niche; obesity; perivascular cells; stem cells.

Figure 1.. Adipose Tissue Organogenesis.

White adipose tissues are formed embryonically and postnatally. A variety of tools have been used to broadly identify early embryonic markers of adipose tissue, such as Myf5, Pax3, and Prx1. Around embryonic day (E)13.5, subcutaneous inguinal and periscapular adipose tissues are specified, patterned, and formed by more restrictive adipose lineage markers, such as PPARγ, adiponectin, and Pref-1. As embryogenesis continues (E18.5), the retroperitoneal adipose depot becomes specified, patterned, and formed. Both the perigonadal and mesenteric white adipose tissues are specified postnatally, beginning at postnatal day 2 (P)2 and ending near P20. Within the first month of life, all adipose depots are specified, formed, lipid filled, and functional. Designation of white adipose depots: IGW, Inguinal; MSW, mesenteric; PGW, perigonadal; PSCW, periscapular; RPW, retroperitoneal.

Figure 2.. Adult Adipose Tissue Homeostasis and Beiging.

White adipocytes formation: adult white adipocyte progenitor cells (APCs) emanate from different lineages than do developmental APCs. However, adult APCs are specified at or near embryonic day (E)10.5; these cells then undergo a rostral–caudal migration throughout embryogenesis, eventually arriving at the adipose depots at approximately postnatal day (P)30. At P30, adult E10.5-specified APC then occupy vascular niche positioning and express mural cell and APC markers. Under homeostatic and adipogenic cues, these cells then transition from the blood vessel niche as they differentiate into mature unilocular white adipocytes. Beige/brite adipocyte formation: in cold-stimulated adult mice, vascular residing alpha smooth muscle actin (SMA)+ beige/brite progenitor cells leave their perivascular niche and differentiate into beige/brite adipocytes. The relation between adult vascular-residing white APC and vascular-residing beige/brite adipocyte progenitors is currently unknown, as is the embryonic specification of beige/brite progenitors.